tbuckley/cabot-search huggingface dataset:
Attachment avoidance and anxiety impacting dyadic coping and communication in patients with metastatic sarcoma and their family caregivers.
Authors: Courtney Daum, Jonathan Singer, Sydnie Schneider, Megan J. Shen, Elizabeth Trice Loggers
Journal: Journal of Clinical Oncology (2023)

e24002 Background: In research, how people act in close relationships is described as “attachment styles” which are composed of multiple attachment style dimensions (ASDs). Attachment avoidance is characterized by the need to isolate from the relationship (i.e. withdrawing and increased independence) while attachment anxiety is defined as needing reassurance and higher dependence. These two insecure ASDs are correlated with reduced quality of life for cancer patients (PT) and the family caregivers (CG). In ovarian cancer, PT and CG ASDs were correlated to dyadic coping, however 27% of PTs were disease-free. Attachment insecurity may be exacerbated by active treatment and uncertain prognosis. Therefore, we investigated the relationship between ASDs, and CG and PT reported dyadic coping and illness-specific communication. Methods: Metastatic sarcoma PTs and their CGs were recruited prospectively for a longitudinal, survey study investigating dyadic coping at Fred Hutchinson Cancer Center from Feb. 2022 – Dec. 2022. Participation rate for eligible PTs was 42% and 68% for CGs. Results are of participants who identified as intimate partners (individuals and dyads were allowed to participate). Attachment avoidance and attachment anxiety were measured via Relationship Structures Questionnaire. Dyadic coping and communication were measured via Dyadic Coping Inventory and Illness-Specific Relationship Talk (ISRT), respectively. Results: Sixty-nine participants enrolled: 43 PTs and 26 CGs (25 dyads). Participants were primarily non-Hispanic and white (91% PTs; 85% CG) with mean age 64 years ( SD= 13.1; range = 26-89). 61% of PTs identified as men; 60% of CGs identified as women. CGs with attachment anxiety were more likely to report worse coping and less ISRT, while PTs with attachment anxiety were more likely to report only worse coping (See Table 1). However, PTs with attachment avoidance were more likely to report both worse coping and ISRT. Conclusions: Advance cancer PTs and their CGs with insecure ASDs report worse coping and communication. Screening for insecure ASDs may identify PTs and CGs who would benefit from supportive care, including psychotherapy. Future research should investigate this in a larger, more heterogenous population at earlier in the rare cancer trajectory and the effect of ASDs on PT, CG, and clinician communication. [Table: see text]
Adverse health effects of opioids in survivors of breast cancer after active cancer treatment.
Authors: Reina Haque, Lie H. Chen, Jiaxiao Shi, Zheng Gu, Moira Brady-Rogers, Rowan T. Chlebowski, Rulin Hechter
Journal: Journal of Clinical Oncology (2023)

e24145 Background: Limited data exists about the effects of opioid use in breast cancer survivors post-treatment. Thus, we examined the risk of adverse events associated with opioid use among breast cancers survivors after active cancer treatment. Methods: We assembled a cohort of women diagnosed with in situ, localized, and regional breast cancer 2009-2019 within a large integrated healthcare system in southern California. Data were captured from the tumor registry, electronic health records, and pharmacy database. We examined opioids use in women with breast cancer after one-year post survival and followed them through December 2021. Opioid use after the first prescription was considered. We examined the risk of incident cardiovascular events (stroke, acute myocardial infarction, arrhythmia); lung problems (COPD, pneumonia); fractures; and falls requiring medical attention. Follow-up was censored at membership disenrollment, death, or study’s end (12/31/2021). We calculated the maximum daily morphine milligrams equivalent (MME) dose during follow-up. Incidence rates (per 1000 person-years, PY) of adverse events were calculated, and multivariable analyses were conducted to estimate hazard ratios (HR) associated with time-dependent opioid use based on Cox proportional hazards models. We adjusted for age; breast cancer surgery; adjuvant cancer therapies; BMI; comorbidity; demographics; and psychiatric drugs. Results: The cohort included 33,989 breast cancer survivors (mean age: 62 years, range: 22-106), followed a maximum of 12 years (median: 5.6 years). The cohort was diverse: 12% African American/Black; 14% Asian/Pacific Islander; 22% Latine; 51% White, and 1% other/mixed. A total of 20,311 women (60%) used opioids during follow-up. The median MME during follow-up was 43.0 (IQR: 30.0-75.0). Falls were the most common event, with a dramatically higher rate for opioid user (47.0/1,000 PY) than non-use (21.8/1,000 PY), corresponding to nearly a doubled risk of falls (adjusted HR = 1.8, 95% CI:1.6-1.9). Similarly, adjusted HRs (95% CIs) for lung problems (HR = 1.6, 1.4-1.7); fractures (HR = 2.1, 2.0-2.3); and CV events (HR = 1.6, 1.3-2.0) were all higher for opioid use. Conclusions: Over 60% of breast cancer survivors used opioids post active treatment. We found statistically significant 1.6-2.1-fold increased risks of adverse events (falls, lung problems, fractures and CV events) associated with opioid use. Clinicians must weigh the risk and benefits of treating pain with opioids post-treatment.
Revealing distinct immune landscape in EGFR mutant and EGFR wild type lung adenocarcinoma by using single-cell RNA sequencing.
Authors: Tianwen Yin, Chao Liu, Tianyu Lei, Peiliang Wang, Menglin Bai, Jinming Yu, Feifei Teng
Journal: Journal of Clinical Oncology (2023)

e21008 Background: Non-small cell lung cancer (NSCLC) with EGFR mutations displays heterogeneity in the extent of intratumoral immunocytes infiltration compared to those with EGFR wild types, which may explain their variable responsiveness to PD-1 blockade. Here, we performed single-cell RNA sequencing (scRNA-seq) to unveil the immunescape and heterogeneity of lung adenocarcinoma (LUAD) between EGFR mutant (EGFR-mut) patients and wild type (EGFR-wt) patients. Methods: Eleven EGFR-mut and 7 EGFR-wt NSCLC tumor samples were analyzed. Immune cells (CD45+) were enriched through fluorescence-activated cell sorting (FACS) and subjected to single-cell RNA sequencing (scRNA-seq) using the 10X Genomics platform. Sequencing reads were normalized and analyzed using the R/Seurat package. Cellular components of each sample were determined based on known marker genes. Wilcox test was used to compare promotion by subtype composition and immune cell infiltrates. Results: Different immune cell compositions were observed between EGFR-mut and EGFR-wt LUAD tumor samples. We found EGFR-wt tumors are marked by an enrichment of CCL15+ tumor-associated macrophages(TAMs), which display pro-inflammatory properties and high expressions of TNF-a-signaling genes. In contrast, EGFR-mut tumors exhibit enrichment of SPARCL1+TAMs, which are involved in epithelial-mesenchymal transition (EMT) and angiogenesis. EGFR-wt tumors exhibited enrichment of CD8-Teff-MX1 and Gamma delta T cells, both of which displayed higher cytotoxic and naive features. Moreover, the high expression of Gamma delta T corresponds with a better clinical prognosis. In contrast, CD8-Teff-XCL1 and NKT-FGFBP2 were found enriched in EGFR-mut tumors, both of which contributed to higher exhaustion and decreased cytotoxic function. Additionally, NK-IL32 was found enriched in EGFR-mut tumors, showing a downregulated T cell receptor signaling and stronger exhausted features. The high expression of this subcluster correlated with poor outcomes in LUAD patients harboring EGFR mutation. Conclusions: Our study provided a deeper understanding of the immune landscape of EGFR-mut and EGFR-wt LUAD and gained better insights into the immunological mechanisms involved in the response to ICIs. The results of our study could be instructive for the development of future immunotherapy strategies for NSCLC patients harboring EGFR mutations.
Comparison of mutation detection rate between cell pellet DNA and cell-free DNA from cerebrospinal fluid in patients with advanced lung cancer.
Authors: Shukun Hu, Xue Wang, Suo Peisu, Yingmei Li, Shifu Chen, Yi Zhang
Journal: Journal of Clinical Oncology (2023)

e21014 Background: Liquid biopsy of cerebrospinal fluid (CSF) has been approved to be a promising strategy for molecular pathology testing in patients with lung cancer. Numerous studies showed that CSF-derived DNA can recapitulate the molecular characteristics of metastatic lung cancer. However, differences in mutation detection rate and the overall mutational profile between cell pellet DNA and supernatant cell-free DNA (cfDNA) from CSF in patients with lung cancer have rarely been reported. Methods: Matched CSF cell pellet and supernatant sample sets were selected from 51 lung cancer patients in our sequencing center. CSF was centrifuged (1000g, 10 min) to separate the cell pellet and supernatant components. Cellular DNA and cfDNA were extracted and underwent library preparation procedures for next-generation sequencing respectively. Cut adapter, mapping, fusion calling and cnv calling were performed for sequencing data analysis. Results: At the sample level, gene mutation could be detected in both CSF cell pellet and cfDNA, and the positive detection rate of gene mutation was consistent. The positive percent agreement (PPA) of CSF cfDNA sequencing compared with CSF cell pellet DNA was 93%. At the genetic variation level, 223 gene mutation sites were detected, and the positive rate of gene mutation in the CSF cfDNA (32.51%) was significantly higher than that in the CSF cell pellet (10.74%, p＜0.01). Additionally，the variation rate of less than 1% was defined as the low-frequency mutation range. Results showed that variant allele frequency (VAF) in CSF cfDNA were remarkably higher than those in the CSF cell pellet in both low-and high-frequency mutation ranges ( p＜0.01, p＜0.01). Conclusions: Both cell pellet DNA and cfDNA isolated from CSF can be used for molecular subtyping of lung cancer. Given that CSF is inevitably contaminated with blood cells in clinical procedures, the dynamic range of tumor cells in CSF could be quite large. CSF cfDNA better recapitulate the mutational status and is recommended to consider first for liquid biopsy in advanced lung cancer with brain metastases or suspicious brain metastases. Key words: Next-generation sequencing; CSF; cell pellet DNA; cfDNA; advanced lung cancer.
Long-term outcome for patients with advanced non‒small-cell lung cancer treated by autologous cytokine-induced killer (CIK) cell immunotherapy in combination with sintilimab plus chemotherapy: NSCLC-CCICC-002.
Authors: Liang Liu, Li Zhou, Xiubao Ren, Weihong Zhang, Yanjuan Xiong
Journal: Journal of Clinical Oncology (2023)

9096 Background: Autologous cytokine-induced killer (CIK) cell immunotherapy in combination with Sintilimab demonstrated robust antitumor activity and safety in the phase Ib CCICC-002 study (NCT03987867) of Non‒Small-Cell Lung Cancer. Long-term outcomes in patients are reported herein. Methods: Systemic therapy naïve patients received platinum-based doublet chemotherapy, Sintilimab (PD1 inhibiter), and CIK cells every 3 weeks for 4 cycles, then maintenance treatment with Sintilimab in squamous and with Sintilimab plus pemetrexed in non-squamous NSCLC until disease progression or unacceptable toxicity or two years. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. OS and PFS were based on immune-related response criteria by investigator assessment (data cut-off, January 31, 2023). Results: From May 2019 to Jan 2021, CCICC-002 enrolled 33 patients（19 squamous, 14 non-squamous NCSLC; 1 patient was excluded because the second biopsy revealed EGFR mutation) aged 46-73 years with median follow-up was 31.4 months (range, 7.6-44.4 months). Estimated 3-year OS was 51.8% in all patients; median OS was not reached (95% CI, 26.6 months-not reached) in all patients. In subgroups, median OS was 27.6 months (95% CI, 13.4 months-not reached) in squamous NCSLC and not reached (95% CI, 29.9 months-not reached) in non-squamous NCSLC, respectively. Median OS was not reached (95% CI, 27.6 months-not reached) in PD-L1 positive patients and 28.3 months (95% CI, 15.6 months-not reached) in PD-L1 negative patients, respectively. Estimated 3-year PFS rate was 27.5% and median PFS was 17.9 months (95% CI, 8.2-26.5 months) in all patients. Median PFS was 17.3 months (95% CI, 5.0-24.0 months) in squamous NCSLC and 22.4 months (95% CI, 5.7 months-not reached) in non-squamous NCSLC, respectively. Median response duration was 18.7 months (95% CI, 10.1-27.6 months). 30.3% of patients were ongoing at data cut-off, and the longest response was ongoing at 41.3 months. 1 of the 5 CMR (complete metabolic response by PET-CT) patients experienced disease progression during observation. Treatment-related AEs (TRAEs) occurred in 94.0% of patients and resulted in study discontinuation in 7.8%, and 15.2% experienced grade 3/4 TRAE. Conclusions: This long-term analysis of CCICC-002 represents the longest follow-up for CIK to date and confirms the durable antitumor activity and tolerability of CIK cells therapy in combination with Sintilimab plus chemotherapy in advanced NCSLC. Further studies are warranted to confirm these preliminary results. Clinical trial information: NCT03987867 .
Evaluating knowledge, attitudes, and practices toward breast cancer and breast cancer screening among females in Arab countries of the Middle East: A systematic literature review.
Authors: Laith Theeb, Alaa Tarazi, Mohammad Al-Kasaji, Hamza Alduraidi
Journal: Journal of Clinical Oncology (2023)

e18761 Background: Among all types of cancer, breast cancer (BC) is the most diagnosed cancer in women and is the leading cause of cancer-related deaths in females globally. Developing countries possess approximately 60% to 70% of all worldwide breast cancer deaths. Despite the increasing efforts to expand awareness and encourage screening, breast cancer is still the most frequently diagnosed form of the disease in Arab countries. In this study, we aim to systematically review the knowledge, attitudes, and practices of middle-eastern Arab women toward the recognition of early breast cancer symptoms, risk factors, and screening. Methods: A literature search was conducted on PubMed and Scopus to identify relevant literature. Search terms included “Knowledge” OR “attitude” OR “practice” AND “breast cancer” AND “Arab region” OR “middle east region”, and other relevant and equivalent terms. All English language studies which achieved the inclusion criteria were included. Each article was independently screened by two researchers in two levels (title/abstract and full-text screening). Data extracted included, but was not limited to, country, study design, study population, sample size, level of knowledge, attitudes, practices, conclusions, and limitations for each study. Results: Out of the 1182 publications identified, 14 cross-sectional studies were included with respondents aged 15 and above. Study populations varied from females attending healthcare centers, to country residents and students. Five studies reported the level of overall BC knowledge, where respondents with low levels of knowledge ranged from 19.7% to 67%. The most chosen risk factors for BC were personal or family history (n = 5), and prior radiation (n = 2). A breast lump or mass was the most chosen warning sign (n = 5), followed by an armpit lump (n = 2). Regarding screening, women who had ever performed breast self-examination (BSE) ranged from 30.3% in Yemen to 57.5% in Oman, while those who consistently performed BSE ranged from 17.4% to 27.9%. Women who had ever undergone mammography ranged from 1.6% to 40%. Barriers to screening included system-related barriers (n = 2), feeling healthy (n = 2), fear of the results (n = 2), and others. Better screening practices were mostly associated with a higher level of education (n = 5), and personal or family history (n = 4). Conclusions: The majority of Arab women in the middle east had heard about breast cancer, but had a low level of knowledge, attitudes, and practices toward breast cancer and its screening methods, which was also variable among different counties. Multiple barriers to screening were found. Such findings can raise the need for programs that elevate knowledge, and provide accessible screening programs that solve for the barriers to screening in the Arab region.
Dynamics of multidisciplinary teams in the Arab world.
Authors: Riham H. AbdelAziz, Marwa Abdelsalam, HebatAllah Mahmoud Bakri, Radwa Fawzy Ahmed
Journal: Journal of Clinical Oncology (2023)

e18753 Background: Multidisciplinary teams (MDTs) are helpful in making clinical decisions and improving patients’ care. This study aims at describing the situation in the Arab world, probing the logistics of cancer patients' referral to MDTs, and highlighting the challenges facing them. Methods: This cross-sectional study via an online pre-tested self-administered survey targeted oncologists and non-oncologists across the Arab world. Results: The survey included 435 participants from 18 Arab countries (317 were oncologists and 118 were non-oncologists). Among the non-oncologists, 67% were involved in diagnosis and management of newly diagnosed cancer patients, 73.5% had specific patient referral criteria in their countries: upon suspected imaging (36%) or proved biopsy results (26%). However, only 36% discuss these patients regularly in MDTs, and 55 out of the 118 do not attend MDT clinics as 47% of them were not invited to MDTs and 13% have a diagnostic role only. Similarly, oncologists thought non-oncologists usually refer suspected patients to oncologists/MDTs upon: suspected imaging (52%), malignant biopsy results (48%), or both (43%). On the other hand, oncologists refer patients to non-oncologists either due to patients’ comorbidities (59%) or upon MDT decision (43%). The results indicated 57% of oncologists discuss suspected patients in MDTs. Among all MDT clinics attendants, 60% had recognized MDTs in their centers. Nevertheless, the majority do not have MDTs for all subspecialties. Moreover, 53% indicated that suspected patients are not directly referred to MDTs; and only 27% indicated they always manage cancer patients upon MDT decision. The majority agreed that surgical, radiation, medical or clinical oncology, radiology and pathology attend MDT clinics. Contrarily, only 5%, 11%, 10%, 2%, 16%, 10% and 13% indicated that psychiatry, nutrition, palliative care, physiotherapy, clinical pathology, specialized nurses and clinical pharmacy attend MDT clinics. Results showed also 94% thought patients benefit of MDTs. The participants’ main consensus upon MDTs benefit was providing accurate treatment recommendations (83%), better clinical decision (70%), and improving team competence (53%). The participants thought the challenges facing MDTs were mainly irregular attendance of physicians (55%), the large number of patients presented in MDTs (41%) and absence of some specialties in MDTs, which means referring patients directly to them (37%). Conclusions: Most institutes have MDTs, but they mainly discuss few subspecialties. Moreover, only 27% of the surveyed physicians indicated they always manage cancer patients upon MDT decision. Additionally, the majority indicated that mainly oncologists, radiologists, and pathologists attend the MDTs. However, other specialties are sorely underrepresented. These discrepancies between MDT logistics through the Arab Countries are deemed a challenge to MDT practice and patient outcomes.
Clinical outcomes of soft tissue sarcoma in the Philippines: A single-center experience.
Authors: Omar Paningbatan Maaño, Agnes Evangelista Gorospe, Anna Marie Pascual-Panganiban
Journal: Journal of Clinical Oncology (2023)

e23549 Background: Soft-tissue sarcomas (STS) are a heterogeneous group of uncommon tumors that account for less than 1 percent of all adult malignant tumors. Data are scarce in the Asia-Pacific region, especially in the Philippines. This study aims to evaluate the epidemiology and clinical outcomes of STS from a private tertiary hospital in the Philippines. Methods: All adult patients treated at St. Luke’s Medical Center (SLMC), Quezon City and Global City, between January 2010 and December 2020 were reviewed. Continuous variables are described in median and categorical variables are described in count and percentage. Kaplan-Meier curves for overall survival (OS) and recurrence-free survival (RFS) were compared by the Log-Rank test. Results: One hundred eighty-seven patients diagnosed with STS were eligible for the study. The median age at diagnosis was 53 years old; the majority were male (54.55%). The most common histologic subtypes were liposarcoma (19.79%), pleomorphic sarcoma, undifferentiated (16.58%), and leiomyosarcoma (11.76%). Most were diagnosed with localized disease (90.9%), with the lower extremities (44.39%) as the most common primary site. The median tumor size was 10.3 cm, primarily high grade (46.52%). Nodal involvement on diagnosis was 4.28%. Twelve patients (6.42%) presented with de novo metastasis; lung (45%) was the most common site. The majority had surgery (81.82%) on the primary tumor, with 56.86% achieving R0. Eighty patients (42.78%) had radiotherapy; the majority were given post-operatively (N = 60). Sixty-three patients (33.68%) received systemic therapy. Out of 170 patients with localized disease, 70 (40%) had disease recurrence, mostly local recurrence (57.14%). The 3-year OS and RFS were 58.67% and 55.20%, respectively, for the entire cohort; for localized disease was 95.06%. There was a statistical difference in OS between distant vs local recurrence (23.28% vs 49.11%)(p &lt; 0.001), nodal involvement (p = 0.041), surgery (p &lt; 0.001), and radiotherapy (p = 0.001). Conclusions: Most STS seen and diagnosed in SLMC is mostly localized disease but with lower rates of resection than in other countries in the Asia-Pacific region. The clinicopathologic features, treatment modalities received, histological subtype, and primary anatomical site are similar to other data. The low survival rate may be attributed to the site of recurrence, nodal involvement, and treatment pattern received.